1. You are the Key to HPV Cancer Prevention Understanding the Burden of HPV Disease, the Importance of the HPV Vaccine Recommendation, and Successfully Communicating about HPV Vaccination Speaker Name Speaker Title Speaker Affiliation {Updated June 25, 2015; Replace with date of Presentation}

2. Disclosure  Please add any financial disclosures or conflicts of interest to this slide

3. Objectives 1. Define the importance of HPV vaccination for cancer prevention and the rationale for vaccinating at ages 11 or 12. 2. List the recommendations for HPV vaccine for girls and for boys. 3. Provide useful and compelling information about HPV vaccine to parents to aid in making the decision to vaccinate. 4. Locate resources relevant to current immunization practice.

4. HPV INFECTION & DISEASE Understanding the Burden

5. HPV Types Differ in their Disease Associations Mucosal sites of infection Mucosal sites of infection Cutaneous sites of infection Cutaneous sites of infection ~ 80 Types “Common” Hand and Foot Warts “Common” Hand and Foot Warts ~40 Types Genital Warts Laryngeal Papillomas Low Grade Cervical Disease Genital Warts Laryngeal Papillomas Low Grade Cervical Disease Low risk (non-oncogenic) HPV 6, 11 most common High risk (oncogenic) HPV 16, 18 most common Cervical Cancer Anogenital Cancers Oropharyngeal Cancer Cancer Precursors Low Grade Cervical Disease Cervical Cancer Anogenital Cancers Oropharyngeal Cancer Cancer Precursors Low Grade Cervical Disease

6. HPV Infection  Most females and males will be infected with at least one type of mucosal HPV at some point in their lives  Estimated 79 million Americans currently infected  14 million new infections/year in the US  HPV infection is most common in people in their teens and early 20s  Most people will never know that they have been infected Jemal A et al. J Natl Cancer Inst 2013;105:175-201

7. Every year in the United States 27,000 people are diagnosed with a cancer caused by HPV That’s 1 case every 20 minutes

8. Cancers Caused by HPV, U.S. CDC, United States Cancer Statistics (USCS), 2006-2010 Cancer site Average number of cancers per year probably caused by HPV† Percentage per year MaleFemaleBoth Sexes Anus1,4002,6004,00091% Cervix010,400 91% Oropharynx7,2001,8009,00072% Penis7000 63% Vagina0600 75% Vulva02,200 69% TOTAL9,30017,60026,900

9. New Cancers Caused by HPV per Year United States 2006-2010 CDC, United States Cancer Statistics (USCS), 2006-2010 Women (n = 17,600) Anus n=2,600 15% Cervix n=10,400 59% Vagina n=600 3% Vulva n=2,200 13% Oropharynx n=1,800 10% Men (n = 9,300) Anus n=1,400 15% Oropharynx n=7,200 77% Penis n=700 8%

10. Cervical Cancer  Cervical cancer is the most common HPV- associated cancer among women  500,000+ new cases and 275,000 attributable deaths world-wide in 2008  11,000+ new cases and 4,000 attributable deaths in 2011 in the U.S.  37% cervical cancers occur in women who are between the ages of 20 and 44  13% (or nearly 1 in 8) between 20 and 34  24% ( or nearly 1 in 4) between 35 and 44 CDC. HPV–associated cancers—US, 2004–2008. MMWR 2012;61(15):258–261. Cervical Cancer Counts by Age. US Cancer Statistics data from 2010, CDC.gov.

11. HPV-Associated Cervical Cancer Incidence Rates by State, United States, 2006-2010 www.cdc.gov/cancer/npcr

12. U.S. Cervical Cancer Rates by Race and Ethnicity, 2004–2008 Watson et al. MMWR 2012;61:258-261.

13. Without vaccination, annual burden of genital HPV-related disease in U.S. females: American Cancer Society. 2008; Schiffman Arch Pathol Lab Med. 2003; Koshiol Sex Transm Dis. 2004; Insinga, Pharmacoeconomics, 2005 4,000 cervical cancer deaths 10,846 new cases of cervical cancer 330,000 new cases of HSIL: CIN2/3 (high grade cervical dysplasia) 1.4 million new cases of LSIL: CIN1 (low grade cervical dysplasia) 1 million new cases of genital warts 3 million cases and $7 billion

14. Annual Report to the Nation on the Status of Cancer: HPV-Associated Cancers  From 2000 to 2009, oral cancer rates increased  4.9% for Native American men  3.9% for white men  1.7% for white women  1% for Asian men  Anal cancer rates doubled from 1975 to 2009  Vulvar cancer rates rose for white and African- American women  Penile cancer rates increased among Asian men Jemal A et al. J Natl Cancer Inst 2013;105:175-201

15. HPV VACCINE Evidence-Based HPV Disease Prevention

16. HPV Prophylactic Vaccines HPV Virus-Like Particle  Recombinant L1 capsid proteins that form “virus-like” particles (VLP)  Non-infectious and non-oncogenic  Produce higher levels of neutralizing antibody than natural infection

17. HPV Vaccines Currently Licensed in U.S. Bivalent 2vHPV (Cervarix) Quadrivalent 4vHPV (Gardasil) 9-Valent 9vHPV (Gardasil 9) ManufacturerGlaxoSmithKlineMerck HPV Types Included 16, 186, 11, 16, 18 6, 11, 16, 18, 31, 33, 45, 52, 58 Contraindications Hypersensitivity to latex* Hypersensitivity to yeast Dose Schedule 3 dose series: 0, 1, 6 months 3 dose series: 0, 2, 6 months 3 dose series: 0, 2, 6 months * only contained in pre-filled syringes, not single-dose vials

18. HPV Vaccine Comparison These Genital warts ~66% of ~15% of HPV Types Cervical Cervical Cause: CancersCancers

19. Girls & Boys can start HPV vaccination at age 9 Preteens should finish HPV vaccine series by 13 th birthday Plus girls 13-26 years old who haven’t started or finished HPV vaccine series Plus boys 13-21 years old who haven’t started or finished HPV vaccine series HPV Vaccine Recommendation

20. HPV Vaccination is Routinely Recommended  HPV vaccination is recommended for both females and males ages 11-12 years  HPV vaccine series should be completed before the 13 th birthday Routine immunization for 11- and 12-year-olds includes HPV vaccination. Clinicians should recommend HPV vaccine on the same day and in the same way as the other vaccines for preteens. MMWR, August 29, 2014, Vo1 63, #RR05

21. Updated ACIP Recommendations Age  Routine vaccination at age 11 or 12 years*  Vaccination recommended through age 26 for females and through age 21 for males not previously vaccinated  Vaccination recommended for men through age 26 who have sex with men (MSM) or are immunocompromised (including persons HIV-infected) Formulation by gender (assuming availability) 21 *vaccination series can be started at 9 years of age MMWR 2015;64:300-4 9vHPV4vHPV2vHPV Females ✔✔✔ Males ✔✔

22. Updated ACIP Recommendations: Formulations  2vHPV, 4vHPV and 9vHPV all protect against HPV 16 and 18, types that cause about 66% of cervical cancers and the majority of other HPV-attributable cancers in the United States.  9vHPV targets five additional cancer causing types, which account for about 15% of cervical cancers.  4vHPV and 9vHPV also protect against HPV 6 and 11, types that cause genital warts. 22 MMWR 2015;64:300-4

23. Updated ACIP Recommendations: Interchangeability If vaccination providers do not know, or do not have available the HPV vaccine product previously administered, or are in settings transitioning to 9vHPV: For protection against HPV 16 and 18,  Females: Any HPV vaccine product may be used to continue or complete the series  Males: 4vHPV or 9vHPV may be used to continue or complete the series 23 MMWR 2015;64:300-4

24. ACIP Recommendations: Timing of the Series  2vHPV, 4vHPV and 9vHPV are each administered in a 3-dose schedule  Interval between doses 1  2: ~6 weeks (1-2 months)  Interval between doses 1  3: 6 months  If the vaccine schedule is interrupted, the series does not need to be restarted 24 MMWR 2015;64:300-4

25. HPV Vaccination Is Safe, Effective, and Provides Lasting Protection  HPV Vaccine is SAFE  Benefits of HPV vaccination far outweigh any potential risks  Safety studies findings for HPV vaccination similar to safety reviews of MCV4 and Tdap vaccination  HPV Vaccine WORKS  Population impact against early and mid outcomes have been reported in multiple countries  HPV Vaccine LASTS  Studies suggest that vaccine protection is long-lasting  No evidence of waning protection Garland et al, Prev Med 2011; Ali et al, BMJ 2013; Markowitz JID 2013; Nsouli-Maktabi MSMR 2013

26. HPV VACCINE SAFETY

27. cdc.gov/vaccines/parents/infographics/journey-of-child-vaccine.html The Journey of Your Child's Vaccine

28. VAERS: HPV Vaccine Safety Monitoring  Ongoing safety monitoring has shown most reports are non-serious  Among the 7.6% of reports coded as “serious,” most frequently cited possible side effects are headache, nausea, vomiting, and fever  Syncope (fainting) continues to be reported following vaccination among adolescents  Adherence to a 15-minute observation period after vaccination is encouraged 28 MMWR. 2014;63(RR05);1-30.

29. VSD Rapid Cycle Analysis (RCA), 4vHPV  RCA allows VSD to detect adverse events following vaccination in near real time  After approx. 600,000 HPV4 doses among females, no significant risk for any of the pre-specified adverse events after vaccination (including GBS, seizures, syncope, appendicitis, stroke, venous thromboembolism, and allergic reactions) Gee J et al, Vaccine 2011;29:8279-8284.

30. Ongoing HPV Safety Activities at CDC  Review of reports to VAERS to search for unusual adverse events or changing patterns of adverse events  VSD addressing HPV vaccine safety in special populations:  Safety of 4vHPV among males  Inadvertent 4vHPV vaccination during pregnancy  VSD addressing HPV vaccine safety concerns that may arise from case reports and/or the media

31. Non-CDC HPV Vaccine Safety Activities  Post-licensure commitments from manufacturers  Vaccine in pregnancy registries  Long term follow-up in Nordic countries  Official reviews  WHO’s Global Advisory Committee on Vaccine Safety 1  Institute of Medicine’s report on adverse effects and vaccines, 2011 2 1 www.who.int/vaccine_safety/Jun_2009/en/ 2 www.iom.edu/Reports/2011/Adverse-Effects-of-Vaccines-Evidence-and-Causality.aspx

32. Key Findings – CDC and Non-CDC  Venous thromboembolism (VTE) 1  Study evaluating the risk of VTE in vaccinated persons age 9-26 years  Found no increased risk of VTE following 4vHPV  Autoimmune and neurologic conditions 2  Study addressing concerns about autoimmune and neurologic disease following 4vHPV vaccination.  Found no association between 4vHPV vaccination and 16 autoimmune conditions  Injection site reactions and syncope 3  4vHPV vaccination may be associated with skin infections where the shot is given during the two weeks after vaccination and fainting on the day the shot is received  No major safety concerns found 1 Gee et al, Vaccine 2011 2 Chao C et al. J Intern Med 2012 3 Klein NP, et al.. Arch Pediatr Adolesc Med. 2012 Dec; 166(12):1140-8.

33. IOM Review: Syncope & Anaphylaxis  IOM reviewed possible associations between 8 vaccines and adverse health events. Key findings:  Evidence “favors acceptance” of a causal relationship between HPV vaccine and anaphylaxis (rare)  Evidence “convincingly supports” a causal relationship between the injection of a vaccine and syncope  Inadequate evidence was found for causal relationships between HPV vaccination and 12 other specific health events studied Institute of Medicine. The National Academies Press, 2012.

34. 9vHPV Vaccine Safety  Seven pre-licensure studies including 15,000 males and females  Generally well tolerated  Adverse event profile similar to that of 4vHPV across age, gender, race, and ethnicity  More injection-site reactions expected among those who receive 9vHPV

35. HPV VACCINE IMPACT Monitoring Impact of HPV Vaccine Programs on HPV-Associated Outcomes

36. HPV vaccine impact monitoring  Post licensure evaluations are important to evaluate real world effectiveness of vaccines  Population impact against early and mid outcomes have been reported: Genital warts  Australia, New Zealand, Denmark, Sweden, Germany, Quebec, US HPV prevalence  Australia, Norway, Denmark, Sweden, UK, US Cervical lesions  Australia, British Columbia, Denmark, Sweden, US 36

37. NHANES HPV Prevalence Studies  National Health and Nutrition Examination Survey (NHANES) data used to compare HPV prevalence  Before the start of the HPV vaccination program (2003-2006 ) &  From the first 4 years after vaccine introduction (2007-2010)  Results  In 14-19 year olds, vaccine-type HPV prevalence decreased 56% (11.5% in 2003-2006 to 5.1% in 2007-2010)  Other age groups did not show a statistically significant difference over time Vaccine effectiveness for prevention of infection was an estimated 82% Markowitz, et al. J Infect Dis 2013

38. Flagg, et al. AJPH 2013 10-14 35-39 15-19 30-34 25-29 20-24 Prevalence per 1000 Person-years Anogenital wart prevalence, female private insurance enrollees, U.S., 2003-2010

39. Proportion of Australian born females and males diagnosed as having genital warts at first visit, by age group, 2004-11 Ali, et al. BMJ 2013 Impact of HPV vaccination in Australia Females Males 39

40. Systematic Review and Meta-Analysis: Population-Level Impact of HPV Vaccination  Review of 20 studies in 9 high income countries  In countries with >50% coverage, among 13-19 yr olds  HPV 16/18 prevalence decreased at least 68%  Anogenital warts decreased by ~61%  Evidence of herd effects  Some evidence of cross protection against other types Drolet et al. Lancet Infect Dis 2015 40

41. Challenges in Monitoring HPV Vaccine Impact on Cervical Lesions  Detected through cervical cancer screening  Changing screening recommendations  Lack of cervical cancer screening registries in some countries  Incomplete linkages with vaccination registries 41

42. HPV Vaccine Duration of Immunity  Studies suggest that vaccine protection is long-lasting; no evidence of waning immunity  Available evidence indicates protection for at least 8-10 years  Multiple cohort studies are in progress to monitor the duration of immunity

43. HPV VACCINE COVERAGE United States HPV Vaccine Three-Dose Coverage Among Girls in High-Income Countries

44. Adolescent Vaccination Coverage United States, 2006-2013 MMWR 2014; 63(29);625-633.

45. Impact of Eliminating Missed Opportunities by Age 13 Years in Girls Born in 2000 Missed opportunity: Healthcare encounter when some, but not all ACIP-recommended vaccines are given. HPV-1: Receipt of at least one dose of HPV. MMWR. 63(29);620-624.

46. HPV Vaccine Series Initiation Girls 13-17 Years, by State, 2013 MMWR. 63(29);620-624.

47. FRAMING THE CONVERSATION Talking about HPV vaccine

48. Clinicians Underestimate the Value Parents Place on HPV Vaccine Adapted from Healy et al. Vaccine. 2014;32:579-584.

49. Give a Strong Recommendation to Receive HPV Vaccine at Ages 11 or 12  A strong recommendation from you is the main reason parents decide to vaccinate  Many moms in focus groups stated that they trust their child’s doctor and would get the vaccine for their child as long as they received a recommendation from the doctor MMWR 2014; 63(29);625-633; Unpublished CDC data, 2013.

51. Make an Effective Recommendation  Same way: Effective recommendations group all of the adolescent vaccines Recommend HPV vaccination the same way you recommend Tdap & meningococcal vaccines.  Same day: Recommend HPV vaccine today Recommend HPV vaccination the same day you recommend Tdap & meningococcal vaccines. Unpublished CDC data, 2013.

52. If a parent were hesitant… AskClarify & restate their concerns to make sure you understand Acknowledge Emphasize it is the parents’ decision. Acknowledge risks and conflicting information sources. Applaud them for wanting what is best for their child. Be clear that you are concerned for the health of their child, not just public health safety. Advise Clarify their concerns to make sure you understand and are answering the question they actually care about. Allow time to discuss the pros and cons of vaccines. Be willing to discuss parents’ ideas. Offer written resources for parents. Tailor your advice using this sheet or CDC’s Tips & Time Savers. Remember Declination is not final. The conversation can be revisited. End the conversation with at least 1 action you both agree on. Because waiting to vaccinate is the risky choice, many pediatricians ask the parent to sign a Declination Form

53. Some Parents Need Reassurance  Many parents simply accept of this bundled recommendation  Some parents may be interested in vaccinating, yet still have questions. Interpret a question as they need additional reassurance from YOU, the clinician they trust with their child’s health care  Ask parents about their main concern (be sure you are addressing their real concern) Unpublished CDC data, 2013.

54. Clinicians can give a strong and effective HPV vaccine recommendation by announcing: Sophia is due for three vaccines today. These will help protect her from meningitis, HPV cancers, and pertussis. We’ll give those shots at the end of the visit.

55. If main concern is “Why does my child need this vaccine” try saying: HPV vaccine is very important because it prevents cancer. I know we’d like to protect Maureen from cancer and I’d feel better if she got her first dose of the HPV vaccine series today.

56. If main concern is “My daughter will wait for marriage/won’t be exposed”, try saying: HPV is so common that almost everyone will be infected at some time. When your daughter marries, she could catch HPV from her husband. He might have been infected before he ever met her.

57. If main concern is “why now, let’s wait until child is older,” try saying: HPV vaccine produces a more robust immune response in preteens than in older teens which is why I recommend starting the HPV vaccine series today.

58. If main concern is “HPV vaccine will be a green light for sex,” try saying: Studies have shown that getting the HPV vaccine doesn’t make kids more likely have sex, or to have sex at a younger age.

59. If main concern is “would you give it to your child,” try saying: Yes, I gave it to my child (or grandchild, etc) because I think preventing cancer is very important.

60. If main concern is “side effects,” try saying: Vaccines, like any medication, can cause side effects. With HPV vaccine most are mild, primarily pain or redness in the arm. This should go away quickly. HPV vaccine has not been linked with any serious or long-term side effects.

61. If main concern is “possible effects on fertility,” try saying: There is no data to suggest that getting HPV vaccine will have an effect on future fertility. However, persistent HPV infection can cause cervical cancer and the treatment of cervical cancer can leave women unable to have children. Even treatment for cervical pre-cancer can put a woman at risk for problems with her cervix during pregnancy causing preterm delivery or problems.

62. Before leaving the exam room, remind parents when to come back. Try saying: To work, Robert needs the full HPV vaccine series, so... Please make sure to make appointments for the next shot on the way out, and put that appointment on your calendar before you leave the office today!

63. Increase the number of target patients who come in & leave vaccinated 1. Align office policy with mission – e.g., immunize at every opportunity 2. Align communication with mission 3. Standing orders 4. Prompt the person who is supposed to order the vaccine  Nursing personnel  EHR  Both

64. Be sure everyone in the office understands the mission Human stories often influence people more than statistics To understand the human stories behind HPV, listen to survivors  Shot By Shot  Unprotected People on www.immunize.org

65. Standing orders  Empower non-physician personnel to vaccinate patients (after assessing for specific contraindications) without direct physician involvement  Practices should have on file preapproved orders to vaccinate  Templates available for all routine vaccines at www.immunize.org/standing-orders/ www.immunize.org/standing-orders/  To save physicians time, staff have to be aware of the standing orders and be trained to use it

66. Review Question #1 HPV vaccine is recommended for the following persons: A. All adolescents at the 11 to 12 year old visit. B. Females only at the 13 year old visit. C. Males only at the 11 to 12 year old visit. D. Females only at the 11 to 12 year old visit.

67. Review Question #1 HPV vaccine is recommended for the following persons: A. All adolescents at the 11 to 12 year old visit. B. Females only at the 13 year old visit. C. Males only at the 11 to 12 year old visit. D. Females only at the 11 to 12 year old visit.

68. Review Question #2 Why should males receive HPV vaccine? A. Prevention of infection with HPV types 6, 11, 16, 18. B. Prevention of genital warts caused by HPV types 6 and 11. C. Prevention of anal cancer caused by HPV types 16 and 18. D. All of the above.

69. Review Question #2 Why should males receive HPV vaccine? A. Prevention of infection with HPV types 6, 11, 16, 18. B. Prevention of genital warts caused by HPV types 6 and 11. C. Prevention of anal cancer caused by HPV types 16 and 18. D. All of the above.

70. Review Question #3 Which of the following HPV vaccine recommendations for a child aged 11 or 12 years is the most likely to be successful? A. Ask parent if child is sexually active and then discuss importance of HPV vaccination. B. Tell parent that their child needs three vaccinations to prevent meningitis, HPV cancers, and pertussis. C. Tell parent about the vaccinations that are mandatory for school entry and ask if they also want HPV vaccine. D. Ask parent if they want to get HPV vaccination for their child or wait until the child is older.

71. Review Question #3 Which of the following HPV vaccine recommendations for a child aged 11 or 12 years is the most likely to be successful? A. Ask parent if child is sexually active and then discuss importance of HPV vaccination. B. Tell parent that their child needs three vaccinations to prevent meningitis, HPV cancers, and pertussis. C. Tell parent about the vaccinations that are mandatory for school entry and ask if they also want HPV vaccine. D. Ask parent if they want to get HPV vaccination for their child or wait until the child is older.

72. HPV PORTAL FOR PROVIDERS cdc.gov/vaccines/YouAreTheKey

73. Continuing Education

74. Factsheets for Parents in English & Spanish

75. cdc.gov/vaccines/who/teens/infographic/hpv-cancer-prevention.html Free posters available for ordering in the following sizes: 8.5x11, 11x17, 18x24

76. Want to know when we have new resources and tools? Send us an email to request our newsletter: PreteenVaccines@cdc.gov We can help provide speakers for grand rounds and continuing education events, as well.

77. HPV VACCINE IS CANCER PREVENTION And YOU are the key! #WeCanStopHPV